Neonatal Fever in the Term Infant: Evaluation and Management Strategies

AbstractThe presence of fever in the neonatal period demands urgent evaluation from healthcare providers since signs and symptoms of a serious bacterial infection in this age group can be nonspecific. Current practice guidelines recommend that febrile neonates should be presumed to have a serious bacterial infection and undergo a sepsis evaluation and hospitalization until the results of diagnostic testing are known. However, less than 50% of outpatient practitioners in a recent study followed these recommendations without apparent adverse outcomes even though the rate of serious bacterial infections in the neonatal period is higher than febrile infants 1-3 months of age. In this article we examine various clinical scenarios that healthcare providers confront when caring for febrile neonates, including whether febrile neonates with respiratory syncytial virus are at increased risk for developing a serious bacterial infection and whether diagnostic testing and empiric antiviral therapy for herpes simplex virus should be part of the standard evaluation of febrile neonates. Although the discovery of inflammatory mediators that are elevated during the early stages of infection has the potential to improve diagnostic capabilities in this age group, there is enough evidence to support international guidelines recommending hospitalization and sepsis evaluations in febrile neonates. KEY WORDS: neonate, fever, sepsis, guidelines, infection

Introduction Fever (temperature ≥ 38.0° C) in the neonatal period (≤ 30 days) can be an important underlying cause of severe infection because of the immaturity of the neonatal immune system. In fact, the annual incidence of severe sepsis in United States in children ≤ 19 years of age is highest in neonates (3.60 per 1,000 population) with over a 10% case fatality rate leading to an estimated 1361 deaths per year [1] compared to 1.6 million deaths annually in developing countries [2]. Infections during the neonatal period can also lead to adverse neurodevelopmental outcomes such as cerebral palsy [3, 4]. In 2003, revised evidence-based guidelines recommended that because serious bacterial infections (SBIs) can present in otherwise well-appearing infants [5], febrile infants between 1-28 days of age should be presumed to have an SBI and undergo a complete sepsis evaluation, receive empiric antibiotics and be admitted to the hospital for further monitoring [6]. Recent guidelines from the United Kingdom continue to emphasize the potential risk of serious illness in febrile infants aged 0-3 months and recommend they be seen by a health care professional within 2 hours [7]. Recognizing that SBIs have been demonstrated to occur more frequently in neonates than in infants between 1-3 months of age [8], these guidelines similarly recommend that infants < 1 month of age should be observed in the hospital with empiric antibiotic initiated until the results of blood, urine and cerebrospinal fluid (CSF) are known. These recommendations apply to neonates with a parental report of fever, even if they are afebrile at the time of evaluation, since the rate of SBI is not necessarily lower in these patients [9]. Despite published guidelines, there is wide variation in levels of adherence to these recommendations [6, 10-12]. In a study of 3066 infants 3 months of age and younger, of whom 775 infants were 0-1 month of age, the above guidelines were followed only 45.7% of the time [6]. Hospitalization for rule-out sepsis evaluation in these young infants can be associated with a high level of parental stress, breastfeeding problems and iatrogenic complications [13, 14]. Additionally, 42% of parents in one study would prefer outpatient therapy to being hospitalized for evaluation of febrile infants [13]. A management strategy that avoids hospitalizing every febrile neonate while not missing an SBI that could lead to an adverse outcome is needed. This article will examine the outcomes of...

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